Camlipixant in Refractory Chronic Cough: A Phase 2b, Randomized, Placebo-controlled Trial (SOOTHE).

Abstract

<b>Rationale:</b> There is no broadly accessible treatment for patients with refractory chronic cough, a disease characterized by chronic cough that persists despite treatment for other cough-related etiologies or has no identified underlying cause. <b>Objectives:</b> SOOTHE (NCT04678206), a phase 2b, randomized, placebo-controlled trial, evaluated the efficacy and safety of P2X3 antagonist camlipixant in adults with refractory chronic cough (cough duration, ⩾1 yr; baseline awake cough frequency, ⩾25 coughs/h). <b>Methods:</b> After a single-blind, 16-day placebo run-in, patients were randomized (1:1:1:1) to receive camlipixant 12.5, 50, or 200 mg twice daily or placebo for 4 weeks. The primary endpoint was change from baseline to Day 28 in objective 24-hour cough frequency. Secondary endpoints included cough severity and cough-related quality of life. <b>Measurements and Main Results:</b> Overall, 310 patients were randomized. A statistically significant reduction in placebo-adjusted 24-hour cough frequency was seen in the 50 mg (-34.4%; 95% confidence interval, -50.5 to -13.3; <i>P</i> = 0.0033) and 200 mg (-34.2%; 95% confidence interval, -50.7 to -12.2; <i>P</i> = 0.0047) camlipixant arms. All camlipixant arms showed a trend for greater improvement in cough severity visual analog scale and Leicester Cough Questionnaire scores over placebo. Camlipixant was well tolerated with no serious treatment-emergent adverse events reported. Taste alteration occurred in 4.8-6.5% of patients in camlipixant arms (vs. 0% with placebo); these were usually mild-moderate. <b>Conclusions:</b> Camlipixant treatment reduced cough frequency and improved patient-reported outcomes in patients with refractory chronic cough, with an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT04678206).